Inhibition of immune functions by antiviral drugs

Immune functions were evaluated in vitro for PBMC isolated from healthy donors and cultured with the antiviral agents, 3'-azido-3'-deoxythymidine (AZT), ribavirin, ganciclovir, 2'3'-dideoxyinosine (ddl), or acyclovir. To identify methods for as-sessing the effects of antiviral drugs on immune cells, the PBMC response to mitogens, Con A, or phytohemagglutinin was evaluated from measurements of [Hjthymidine and 11[C-leucine incorporation, cell growth, cellular RNA, DNA, and protein levels, and the PBMC proliferative cycle (i.e., progres-sion from GO-- G1-- S- G2 + M). At clinically relevant concentrations, AZT, ribavirin, or ganciclovir diminished PBMC responsiveness to mitogen. The numbers of proliferating cells in G1, S., and G2 + M phases of the cell cycle, DNA content, and VHjthymidine uptake were decreased in cultures treated with AZT, ribavirin, or ganciclo-vir. AZT or ribavirin but not ganciclovir reduced RNA and protein in the cultures and inhibited cell growth. Whereas AZT, ribavirin, or ganciclovir were antiproliferative, ddI or acyclovir had little, if any, effect on PBMC mitogenesis. The inhibitory effects of antivirals on immune cells may contribute to the immune deterioration observed in patients following pro-longed use of the drugs. (J. Clin. Invest. 1991. 87:1916-1924.) Key words: lymphocytes- virus replication * HIV * immunosup-pression * herpes- viru